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Abstract

Introduction: After myocardial infarction (MI), macrophages infiltrate the infarct zone, play vital roles in infarct healing, and may be therapeutic targets. We showed previously that T1 mapping after labeling monocytes with a T1 shortening contrast agent enables imaging of macrophage infiltration of the infarct zone 4 days after MI. However, while labeled macrophages shorten infarct-zone T1, infarct-related edema counteracts this effect and lengthens infarct-zone T1. We hypothesized that ΔR1 (R1=1/T1), measured as the difference in infarct-zone R1 between labeled and unlabeled mice, would improve measurement of the time course of macrophage infiltration.

Methods: 100 µL of liposomes incorporating gadolinium (GdL) were injected i.v. in 6 mice on day −2. As controls, n=6 mice had no injection of GdL. Reperfused MI was induced on day 0 by a 1 hour occlusion of the left coronary artery. R1 mapping was performed on days −3 and 0 before MI and on days 1, 4 and 7 post-MI. Cine DENSE assessed myocardial strain and Ecc strain > −0.05 defined the infarct zone.

Results: R1 mapping in GdL-labeled mice detected macrophage infiltration on day 4 post-MI (Fig. A, arrows), which was confined to the infarct zone as defined by the strain map (Fig. B, arrows). Elevation of infarct zone R1 was solely observed on day 4 post-MI (*p<0.05 vs. all days, &p<0.05 vs. same day control) (Fig. C). In control mice, edema-related R1 shortening was observed on all days post-MI (Fig. C) and essentially canceled the R1 lengthening due to GdL-labeled macrophages on days 1 and 7. ΔR1, which subtracts the edema-related change in R1 from the change in R1 due to GdL-labeled macrophages, properly depicted the time course of post-MI macrophage infiltration, showing remarkable agreement with prior in vitro histological studies (&p<0.05 vs. same day remote zone) (Fig. D).

Conclusions: Using ΔR1 corrects for the effect of infarct-related edema and improves serial quantitative assessment of post-MI macrophage infiltration.